Alternative Approaches to the Management of Priapism

Alternative approaches to the management of priapism

JD deHoll,1 PA Shin,1 JF Angle2 and WD Steers1

Departments of 1Urology and 2Radiology, University of Virginia School of Medicine, Charlottesville, Virginia, USA

Herein we describe the use of intracavernous methylene blue (MB), a guanylate cyclase inhibitor, or internal pudendal artery embolization for the treatment of priapism. Eleven patients with priapism were treated from 1993±1996. Etiologies of priapism included PGE1/papaverine (3), trazodone (2), and sickle cell disease (1), in the other ®ve cases the cause was unknown. The average duration of priapism was 27 h for all patients (6±72 h). Five patients who failed intracavernous MB or an a-adrenergic agonist, underwent unilateral or bilateral pudendal artery embolization. The average duration of priapism for patients undergoing embolization was 43 h. Sixty-seven percent of the patients treated with MB responded with immediate detumescence. One-hundred percent of patients with priapism secondary to intracavernous injection therapy or trazodone responded. Of the ®ve patients who underwent embolization, 40% achieved immediate pain relief and subsequent detumescence. The three non-responders exhibited a partial detumescence over 47±72 h. After follow-up of one year embolization available for only two patients revealed that one regained potency while the other remained impotent. These results con®rmed that MB is effective for pharmacologically-induced priapism. Embolization is a less invasive option for refractory priapism, although results are less than satisfactory in men with priapism of several days duration.

Keywords: methylene blue; pudendal artery; embolization; Gel-Foam

Introduction agents which cause a rise in cGMP. We have previously reported temporary success with IC Over the last decade advances in understanding the methylene blue for the treatment of priapism.3 physiology and pharmacology of erection have led Methylene blue is widely used topically and to greatly expanded knowledge of the etiology and intravenously. Its has virtually no signi®cant side treatment of priapism.1 Pharmacologically-mediated effects and is rapidly excreted by the kidneys into priapism is more common with the widespread use the urine. Rarely, a slight rise in blood pressure is of intracavernous (IC) therapy for impotence. This seen after systemic administration. The safety adverse event is treated by (IC) a-adrenergic agonists pro®le of MB and its ability to block the effects of such as phenylephrine.2 The search for other non- nitrovasodilators including NO lead to its routine surgical treatments with minimal systemic side use in the treatment of priapism. As an inhibitor of effects has led us to investigate the use of methylene guanylate cyclase, MB is hypothesized to produce blue.3 detumescence by preventing prolonged activation of Neurally-mediated vasodilatation and corporal a cGMP pathway. It may also release norepinephrine cavernosal smooth muscle relaxation produce tu- via free radical formation. mescence.1 Nitric oxide (NO) released from para- Despite the widespread use of a-adrenergic sympathetic nerves activates a guanylate cyclase agonists for priapism, surgical management is often which leads to elevation of cGMP.4±6 GTP or ATP is necessary. The Winter7,8 percutaneous procedure converted to its cyclic monophosphate moieties, and the Al-Ghorab or Quackles shunts are com- which is thought to produce a fall in cytosolic monly performed. The success rates for these calcium causing relaxation of smooth muscle. procedures vary from 50±65%.8,9 Wear et al.10 ®rst Methylene blue (MB) is an inhibitor of guanylate described the treatment of priapism with pudendal cyclase and thereby blocks the smooth muscle artery embolization in 1977. In an effort to avoid relaxation initiated by nitric oxide (NO) or other surgery, which lacks ef®cacy in at least half of the patients, we prospectively subjected all cases of priapism refractory to IC MB or an a-adrenergic Correspondence: Dr WD Steers, University of Virginia Health agonist to pudendal embolization to see if results Sciences Center, Department of Urology, Box 422, Charlottesville, Virginia 22908, USA. were comparable to surgery. The goal of this study Received 16 May 1997; revised 27 June 1997; accepted was to describe and compare two new non-surgical 11 August 1997 treatment regimens for priapism. Alternative approaches to the management of priapism JD deHoll et al 12

Figure 2 Results of intracavernous methylene blue on priapism. Success after methylene blue is de®ned as complete detumescence and pain relief.

Figure 1 Site of action for methylene blue. Corpus cavernosum smooth muscle relaxation can be achieved by nitric oxide acting Patients receiving pudendal artery embolization on guanylate cyclose thereby producing a rise in cGMP. Likewise, underwent diagnostic arteriography of the pelvis PGE1 acting on adenylate cyclse can raise cAMP. cAMP is normally degraded by a phosphodiesterase (probably type 3). with bilateral selective injections of the internal Elevations in these cyclic nucleotides cause relaxation. Papa- pudendal arteries. No arterio-venous ®stulas or verine may enhance relaxation and erections by inhibiting a arterial extravasation was identi®ed. Embolization phosphodiesterase. was performed through a 5F multi-purpose catheter (Cook, Bloomington, IN), advanced to the distal internal pudendal artery or to the level of the Methods common penile artery. In patients with small caliber pudendal arteries, a 3F microcather (Target Ther- apeutics, Fremont, CA) was placed coaxially Eleven patients were treated for priapism between through the 5F catheter. Approximately 1 mmÂ 1993 and 1996. The age range was 22±56 y (mean 1mm62 mm pledgets of Gel-Foam (Upjohn Cio, 37 y). The average duration of priapism for the Kalamazoo, MI) were injected until complete stasis entire group was 7 h (range 6±72 h). Priapism was was achieved. Embolization was bilateral in four of de®ned as prolonged painful tumescence lasting ®ve cases. Staged procedures were separated by 24 h more than 6 h. Etiology for patients were: PGE1 to monitor for detumescence and skin necrosis. (n 2), trazodone (n 2), papaverine (n 1), sickle All patients had bright red blood (BRB) aspirated cell (n 1) and idiopathic (n 5). Five patients were from the corpora during initial treatment. All treated initially at our institution. The remaining six men were referred after unsuccessful treatments by community urologists. In patients without previous therapy. MB was ®rst administered after irrigation and aspiration of the copora. Approximately 50 mg of MB 1/2 ampule) was injected IC and left for 3± 5 min. The MB was then aspirated and light compression was held on the penis for 5 min. MB was administered after aspiration of the blood from the copora cavernosa. Two of the 11 were not given MB due to previous extensive surgery for their priapism. These patients underwent immediate unilateral pudendal artery embolization. Because nearly half the patients presented after lengthy delays with substantial penile edema, effective therapy in these patients was de®ned as a greater than 50% detumescence and relief of pain.

Table 1 Results of pudendal artery embolization for priapism of long duration

Unilateral Bilateral Response embolization embolization

Immediate detumescence 0 2 Figure 3 Representative pudendal arteriography demonstrating Delayed detumescence 1 2 site of embolization. Gel Foam is introduced into the common penile artery. DAP diorsal artery of the penis. Alternative approaches to the management of priapism JD deHoll et al 13 patients underwent angiographically demonstrated Although MB appeared to be without signi®cant dilation of the pudendal artery. An attempt was side effects in our series, penile necrosis has been made to call each of these patients after one year. reported after its used.11 Necrosis has been attributed to free radical generation and tissue ischemia. However, this reported adverse event occurred in a Results patient who had 5 y of intermittent priapism with ®brosis, and occurred one week following an unsuccessful shunt procedure. In addition, the Nine patients were treated with MB. If MB was reported patient received intracavernous a-agonists. ineffective then phenylephrine was administered. Alpha-agonists have been used after MB injection However, no patient failing MB was effectively without ill effect, but this should be done with rescued with an a-adrenergic agonist. Six of nine caution. Alpha-agonists offered no bene®t in cases (67%) patients were cured using MB alone. For drug where MB was unsuccessful. Apparently, either MB induced priapism, 100% of the patients were cured or a-agonists can be used as initial therapy, but if with MB alone. In contrast, only 20% of the either is unsuccessful, additional bene®t from the idiopathic patients were cured with MB, with an other is unlikely. An additional side effect of MB average duration of priapism of 42 h. The primary treatment was a temporary blue discoloration of the side effect was transient mild burning with injection penis. Two patients with priapism due to PGE of the MB. complained of burning sensations of the penis Five patients who failed prior IC therapy and/or following injection of MB, which resolved in 1 h. surgical shunt procedures underwent embolization Within 1 year after successful MB treatment, three of the pudendal artery. None of these patients gave a patients regained baseline erectile status. Oral history of trauma to the perineum or penis. The agents such as a-agonists can be considered, but average duration of priapism in this refractory group recent concerns regarding hypertension and cardiac was 43 h. All patients in the embolization series had arrhythmias may limit their usage. It is unknown aspiration of bright red blood from the corpora. whether oral MB would be effective. Dilatation of the pudendal artery and the distal If pharmacologic therapy fails, the decision cavernous artery was seen on arteriography. In one whether patient should undergo a shunt procedure patient unilateral embolization failed to elicit or pudendal artery embolization is unclear. A detumescence but provided relief from pain. This reported 50% failure rate for surgery prompted us patient did not desire additional treatment. Two of to evaluate the use of pudendal artery emboliza- the four remaining patients achieved detumescence tion. There have been 22 previously reported cases after bilateral embolization. Adverse effects from the of pudendal artery embolization for the treatment embolization were limited to gluteal pain. of priapism.3,10,12±28 Authors recommend the use of Only ®ve of 11 patients were available for follow- embolization for `high ¯ow priapism' attributed to up at one year after treatment. Of three patients who trauma or A-V ®stulas. In these situations, nearly were cured by MB, all reverted to their baseline 100% ef®cacy with unilateral or bilateral emboliza- erectile status. One patient who had bilateral tion has been reported. However, the classi®cation embolization had regained potency. Another patient of high and low ¯ow priapism is problematic and with priapism lasting ten days remained impotent. embolization has been effective in`low ¯ow rates'.3,16 Three patients died of unrelated causes. The Arteriography revealed dilation of internal puden- remaining two patients could not be located. dal arteries in all of our cases. The corporal aspirate, even if initially dark venous blood, eventually became bright red with continued aspiration. It can Discussion be speculated that once priapism develops, vasodi- lation continues due to ischemia, acidosis or hypoxia. Management of priapism is problematic. While Embolization was performed in ®ve patients initial therapy with intracavernous vasoconstrictor failing medical therapy, the results were poor. agents is recommended, the roles of surgery and Bilateral treatment was necessary to achieve detu- embolization are unclear. Methylene blue was a safe mescence, but required 4±10 days. Without an and effective treatment for priapism. The etiology untreated control group it is unclear whether similar and duration of priapism were the strongest pre- results would have been obtained without therapy. dictors of success with intracavernous MB. The lack Nevertheless, immediate pain relief was achieved of ef®cacy of MB in patients failing previous and remains the primary indication for this ap- therapies did not preclude success if administered proach. One of the two patients cured by bilateral early in the course of priapism. MB caused detu- embolization was able to obtain normal erections mescence in patients with priapism following within six months following arteriography. Presum- intracavernous prostaglandin E-1, suggesting inter- ably, this patient either had recanalization of the ference with cAMP mechanisms. internal pudendal arteries or generous collateral Alternative approaches to the management of priapism JD deHoll et al 14 supply from the external pudendal branch of the 7 Winter CC. Cure of idiopathic priapism. New procedure for femoral artery. Indeed, the failure of bilateral creating ®stula between glans penis and corpora cavernosa. Urol 1976; 8: 389. pudendal embolization to eradicate priapism may 8 Winter CC, McDowell G. Experience with 105 patients with be explained on the basis of collateral blood ¯ow priapism: update review of all aspects. J Urol 1988; 140: 980. through this external pudendal artery via the 9 Kulmala R. Treatment of priapism: primary results and femoral artery. Repeat pudendal arteriography has complications in 207 patients. Ann Chirurgiae et Gynae- been performed one year after a patient has cologiae 1994; 83: 309±314. 10 Wear JB, Crummy AB, Munson BO. A new approach to the successful treatment with Gelfoam embolization at treatment of priapism. J Urol 1977; 117: 252±254. our institution. This patient presented with recur- 11 Mejean A et al. Letter to the Editor. J Urol 1993; 149: 1149. rent priapism. The repeat arteriogram revealed 12 Cohen GS et al. Selective arterial embolization of idiopathic recanalization of the distal pudendal artery. We priapism. Cardiovas Intervent Rad 1996; 19: 47±49. believe patients having renal allografts, aortofemoral 13 Kim SC, Park SH, Yang SH. Treatment of posttraumatic chronic high-¯ow priapisms by superselective embolization of or femoral bypass surgery should not undergo cavernous artery with autologous clot. J Trauma 1996; 40(3): pudendal artery embolization. 462±465. 14 Kuwahara M et al. 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